P2X2 Receptor Deficiency in Mouse Vestibular End Organs Attenuates Vestibular Function

Abstract

P2X₂ receptors are ligand-gated cation channels activated by extracellular ATP that modulate neural transmission in various neuronal systems. Although the function and distribution of P2X₂ receptors in the cochlea portion of the inner ear are well established, their physiological role in the vestibular portion is still not understood. Therefore, we investigated P2X₂ receptor localization in the peripheral vestibular portion, and assessed their physiological function in vivo using P2X₂ receptor knock out (P2X₂-KO) mice. Histological analysis revealed that P2X₂ receptors were localized on the epithelial surface of supporting and transitional cells of the vestibular end organs. To examine vestibular function in P2X₂-KO mice, we conducted behavioral tests and tested the vestibulo-ocular reflex (VOR) during sinusoidal rotations. P2X₂-KO mice exhibited significant motor balance impairment in the balance beam test. VOR gain in P2X₂-KO mice was significantly reduced, with no decrease in the optokinetic response. In conclusion, we showed that P2X₂ receptors are mainly localized in the supporting cells of the vestibular inner ear, and the loss of P2X₂ receptors causes mild vestibular dysfunction. Taken together, our findings suggest that the P2X₂ receptor plays a modulatory role in vestibular function.

Keywords: ATP; P2X(2)-KO; VOR; inner ear; supporting cell; vestibular dysfunction.